Targeting COVID-19 (SARS-CoV-2) main protease through phytochemicals of Albizia lebbeck: molecular docking, molecular dynamics simulation, MM–PBSA free energy calculations, and DFT analysis

The unforeseen occurrence of the new coronavirus disease (COVID-19) has affected eight million people worldwide. There is an urgent need to develop new drugs to combat the infection due to non-availability of therapeutic options. The present study describes the potential of phytochemicals of Albizia lebbeck to be used as a SARS-CoV-2 M^pro inhibitor by molecular docking using CDOCKER of discovery studio. Based on docking results, four compounds Vicenin 2, Myricetin, Quercetin, and Albigenic acid were studied using 100 ns molecular dynamic simulations to determine conformational stability for all protein–ligand complexes along with Nelfinavir (Positive control). Furthermore, MD-simulation studies supported by standard analysis, e.g. root-mean-square deviation and fluctuation (RMSD, RMSF) and radius of gyration showed significant impact on the structure of Mpro by above four compounds. MM–PBSA energy parameters revealed that binding free energy of Quercetin was more compared to Nelfinavir. Density functional theory studies have been carried out to study HOMO and LUMO which revealed Vicenin 2 was more reactive compared to other compounds and Nelfinavir. Mulliken atomic charges were studied to determine partial charges on the four best molecules obtained after analyzing docking scores. In conclusion, Vicenin 2, Myricetin, and Quercetin have potential to become therapeutic options for treating SARS-CoV-2 infection.